Familial evaluation reveals a distinct genetic cause in a large Spanish family with neurofibromatosis 1 and hypertrophic cardiomyopathy

Gene. 2020 Jul 1:746:144658. doi: 10.1016/j.gene.2020.144658. Epub 2020 Apr 10.

Abstract

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder characterized by café-au-lait spots, intertriginous freckling, and multiple neurofibromas. Classically, it has been described that hypertrophic cardiomyopathy (HCM) may be a cardiovascular manifestation of neurofibromatosis 1, although the relationship between these two entities has not been fully established. We report a large Spanish family carrying a pathogenic truncating variant in NF1 (p.Arg2258Ter) causing neurofibromatosis 1, and a pathogenic missense variant in MYH7 (p. Arg453Cys), causing hypertrophic cardiomyopathy independently. A complete penetrance was observed in both genetic diseases, reinforcing the notion of deleterious effects of both rare variants. According to our report, hypertrophic cardiomyopathy in patients with NF1 should not be considered as part of the clinical spectrum in all cases. A careful and comprehensive assessment, including family evaluation and genetic testing for HCM should be considered as part of the diagnostic work-up in individuals presenting with both phenotypes.

Keywords: Genetics; Hypertrophic cardiomyopathy; Myocardial diseases; Neurofibromatosis 1.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Cafe-au-Lait Spots / genetics*
  • Cardiac Myosins / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Codon, Terminator*
  • Family
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Myosin Heavy Chains / genetics*
  • Neurofibromatosis 1 / genetics*
  • Neurofibromin 1 / genetics*
  • Pedigree
  • Spain

Substances

  • Codon, Terminator
  • MYH7 protein, human
  • NF1 protein, human
  • Neurofibromin 1
  • Cardiac Myosins
  • Myosin Heavy Chains